This application seeks continued support for the Cell and Molecular Biology Training Program (CMBTP) at Case Western Reserve University. The central goal of the CMBTP is to train highly motivated graduate students to become outstanding independent investigators capable of applying diverse approaches to solve important problems in modern biology. This objective is achieved through four primary mechanisms: 1) original research beginning with a series of laboratory rotations in the first year; 2) rigorous coursework covering fundamental and advanced concepts in lecture/discussion and seminar formats; 3) attending and presenting seminars and journal clubs in diverse disciplines; and 4) organizing and participating in the seminar series and symposia sponsored by the CMBTP. The defining element of the CMB research community is its breadth. Members of the training faculty are investigating a diverse array of research problems in biological systems ranging from single molecules to intact organisms. Consistent with its interdisciplinary philosophy, the CMBTP sponsors events that promote interactions and encourage collaboration among students and faculty from numerous programs and departments. This program pre-dated and was the driving force behind the development of the Biomedical Sciences Training Program (BSTP), a highly effective umbrella mechanism for recruiting Ph.D. students to eleven Ph.D. granting units and overseeing their first year of graduate study. The CMBTP dovetails with the BSTP to provide support for students who have already selected a mentor and Ph.D. program (many trainers are affiliated with >1), and benefits from the integrated approach to research fostered by the BSTP. Training grant policies and key decisions including appointment of trainees and training faculty are made by the Director in consultation with a Steering Committee comprised of representatives from each of the contributing programs. Candidates for support are nominated by their mentors and undergo a rigorous screening process culminating in an interview with the entire Steering Committee that covers both current search and long-term career aspirations. In the course of their training, CMBTP students develop an appreciation for approaches that span traditional disciplinary boundaries and are encouraged to interpret their data from multiple perspectives. The achievements of past and present trainees indicate that the program provides a solid foundation upon which to build a successful independent research career. Support is requested for nine predoctoral student positions in alt years, the same number allocated currently. The research pursued by trainees under the auspices of this training program is aimed at enhancing our understanding of basic cellular processes that are perturbed in disease states including cancer, neurological disorders and metabolic defects. Thus, the award will be used to promote improvements in human health. [unreadable] [unreadable] [unreadable]